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Obstructive Sleep Apnea Contributes to MS Fatigue

Diagnosing and treating OSA may eliminate 11% to 40% of the fatigue attributed to MS

Ricki Lewis, Ph.D.

Some of the fatigue that affects up to 90% of people with MS may be due to obstructive sleep apnea (OSA), according to a recent report in the Journal of Clinical Sleep Medicine from researchers at the University of Michigan (Braley et al., 2014).

Confusing the issue is the high prevalence of OSA in the general population. According to the American Academy of Sleep Medicine, 7% of men and 5% of women have OSA, but the prevalence could be up to 24% for men and 9% for women if individuals without daytime sleepiness are considered. A study by Marta Kaminska, M.D., at Royal Victoria Hospital in Quebec, Canada, and colleagues that compared ambulatory MS patients without a sleep disorder diagnosis to controls found that OSA is over-represented among people with MS. Using polysomnography and multiple sleep tests, they found that 36 of 62 (58%) of MS patients had OSA compared to 15 out of 32 (46%) controls, and that severe fatigue was associated with OSA in MS but not controls (Kaminska et al., 2012). “Fatigue” means lack of energy during the day, not poor ability to fall or stay asleep at night (Neau et al., 2012).

In the current study, Tiffany J. Braley, M.D., M.S., an assistant professor of neurology at the University of Michigan’s Multiple Sclerosis and Sleep Disorders centers, Benjamin M. Segal, M.D., director of the Multiple Sclerosis Center, and Ronald D. Chervin, M.D., M.S., director of the Sleep Disorders Center, designed a questionnaire and gave it to 195 MS patients. The instrument assessed sleep quality, duration, related drug use, daytime symptoms, CPAP (continuous positive airway pressure) use, and symptoms such as pain, tingling, restlessness, anxiety, urinary urgency, twitching, and ease of falling asleep.

The researchers also used assessment scales for sleepiness, fatigue severity, insomnia severity, and a questionnaire called STOP-Bang (an acronym for Snoring, Tired, Observed apnea, Blood Pressure, BMI (>35), Age (>50), Neck circumference (>17 inches for men, >16 inches for women), and Gender). They also considered MS stage, disease duration, drugs, depression, and degree of disability.

The mean age of participants was 47 years, and 66% were female. Their mean disease duration was 10.2 years, 74% had relapsing-remitting MS, and 68% took drugs for MS.

Of the 195 patients, 110 (56%) had increased risk of OSA according to a STOP-Bang score greater than 3. Of the 41 (21%) diagnosed with OSA, 32 were prescribed CPAP, and 17 used it. Patients who reported the greatest fatigue were at higher risk for OSA.

The researchers recommend use of STOP-Bang to identify MS patients who might benefit from a formal sleep study. Although this investigation could not detect causation, the researchers suggested that diagnosing and treating OSA can potentially eliminate 11% to 40% of fatigue attributed to MS.

Key open questions

To what extent does intervention (CPAP) to address OSA ameliorate MS-related fatigue?

Which are the most effective instruments for identifying people with MS who might benefit from a sleep study?

What clinical benefit might derive from treating OSA in MS patients who do not have fatigue?

Disclosures and sources of funding

Drs. Braley, Segal, and Chervin hold or have filed patents with the University of Michigan on treatment for OSA. The study was not industry-funded. Drs. Kaminska, Trojan, and Kimoff received research support from VitalAire Inc. and Philips Respironics, and Dr. Kaminska receives support also from ResMed.

Comments

19 Feb 2014

Marta Kaminska, McGill University Health Centre

In the study, a large proportion of patients had a positive STOP-Bang, which suggests that OSA is underdiagnosed in MS, which our findings also suggest. Since the STOP-Bang has not been specifically validated in MS, its reliability in this context is unknown. The fact that 93% of MS patients known to have OSA had a positive STOP-Bang questionnaire is encouraging but should not be extrapolated to those without known OSA, as this is a potentially very different patient group. The Berlin questionnaire, well-validated in the general population, had poor sensitivity for OSA in MS (Trojan, Mult. Scler. 2009; 15:S54). The STOP-Bang might, like the Berlin questionnaire, underestimate OSA prevalence.

Association between OSA and fatigue in MS has previously been demonstrated in two studies using polysomnography to diagnose OSA. Thus the findings of Braley et al., while not novel, and based only on questionnaire data, provide important additional data linking OSA and fatigue in MS.

Braley et al. found no difference in fatigue in those reporting compliance with CPAP treatment for OSA compared with others. However, this part of their study was underpowered and confounded by lack of objective compliance measurement (in those reporting both good and poor compliance). Other confounders related to fatigue or treatment compliance may have been present.

In another recently published, controlled study (Côté, Mult. Scler. 2012), MS patients were prospectively followed and those treated for sleep disorders (the most prevalent of which was OSA) had significant improvement in fatigue scores. Further work is clearly warranted to more carefully study the effect of OSA treatment on fatigue in MS patients.

Fatigue is a debilitating symptom of MS, associated with OSA. Despite its limitations, the study by Braley et al. does bring to light the fact that OSA is likely highly prevalent in MS and underdiagnosed, and will hopefully spur further research in this area.

Dara A. Trojan, M.D., M.Sc., and John Kimoff, M.D. contributed to this comment.

19 Feb 2014

Timothy Morgenthaler, American Academy of Sleep Medicine

This study demonstrates that the prevalence of OSA, or of being at high risk, is higher in fatigued patients with MS. It adds to literature that has demonstrated a higher prevalence of sleep disorders such as insomnia, restless legs syndrome, and REM sleep behavior disorder.

Fatigue has been difficult to treat well in patients with MS. In contrast, most sleep disorders have effective treatments. This information should prompt patients, and those who care for them, to inquire carefully about the possibility of sleep disorders that might be amenable to disease-directed therapies rather than symptom-oriented care alone.

The study looked at both firm diagnoses of OSA and the likelihood of having significant OSA as judged by a clinical decision tool, the STOP-Bang. This tool was developed to help identify surgical patients at high risk for OSA. It has not been validated in the MS population. Such questionnaires only estimate risk of having OSA. To actually diagnose OSA, one needs a confirmatory test: either in-lab polysomnography or a home sleep test. Nonetheless, using a standardized risk-stratifying questionnaire is probably better than clinical interviews alone, particularly because in some studies of MS patients with OSA, excessive sleepiness has not been as prevalent as it often is in non-MS patients with OSA.